Helping the Brain to Help Itself

Neuron transform: An astroglial cell from a mouse’s brain has been transformed into a type of neuron called an excitatory neuron. The green color marks a molecule specific to excitatory neurons, and the white indicates a molecule critical for synaptic plasticity, a key function in communication between neurons.

Support cells in the brain called astroglia can be turned into functioning neurons, according to a study in this week’s Public Library of Science Biology. Researchers found that they could transform the cells into two different classes of neurons, and that the neurons could form connections with one another in a dish. Although the research is at an early stage, the finding suggests that scientists could someday recruit existing cells in the brain to repair the brain and spinal cord after a stroke, injury, or neurodegenerative disease.

The research team, from the Helmholtz Center and Ludwig-Maximilians University in Munich, had previously shown that it was possible to turn astroglia–star-shaped cells that provide structural support in the brain–into neurons by introducing genes called transcription factors into the cells using a virus. In that study, however, the neurons did not form functioning connections, or synapses. Now the researchers have demonstrated that astroglial cells taken from young mice can be transformed into synapse-forming neurons, and can be directed into two different major classes of neurons.

The addition of one specific genegenerated excitatory neurons, which promote activity in other cells. By adding a different gene, they generated inhibitory neurons, which dampen cell activity. In principle, “you could generate other types of neurons if you choose the appropriate factors,” says study coauthor Benedickt Berninger. For instance, he said, researchers could generate the dopamine-releasing neurons that are destroyed by Parkinson’s disease.

The study adds to growing evidence that certain cell types can be transformed directly into other cell types without first being converted into stem cells. Researchers have previously transformed skin cells into neurons, and one type of pancreatic cell into another. Marius Wernig, a coauthor of the skin cell study and a stem cell biologist at Stanford University, says there’s a growing awareness that it may not be necessary to erase a cell’s existing identity before giving it a new one.

Wernig says that the PLOS Biology paper offers a new strategy for creating neurons that complements the approach of using skin cells. Skin cells, he says, would be more useful for generating a patient’s own cells in a petri dish for transplantation, because a skin sample is easy to obtain. In contrast, this latest study “means that these astroglial cells could be converted in the brain” without the need for a transplant. Berninger says that one of the next challenges is to determine whether these reprogrammed neurons can survive and function in a living brain.

Fortunately, the brain seems to have a ready source of astroglia. When the brain is injured, these cells proliferate, similar to the way the skin repairs itself after a wound. The researchers found they could also derive neurons from injury-induced astroglia taken from the brains of adult mice.